Vaccine development news, FDA actions, manufacturing approaches, and more. 

COVID-19 Update

Catalent announced on Sept. 24, 2020 that it has acquired a manufacturing facility in Bloomington, IN to create a new North American center of excellence for early-phase clinical biologics formulation development and drug product fill/finish services. The $14 million investment includes the acquisition, build-out, and qualification of the facility.

The 23,000 ft2 site, purchased from AB BioTechnologies and its affiliate, features a new Vanrx SA25 aseptic flexible filling line for the filling of lyophilized vials, syringes, and cartridges; formulation development capabilities; quality control laboratories; and controlled temperature storage, a company press release said. Set to be operational in January 2021, the facility will also be integrated with Catalent Biologics’ main Bloomington facility located nearby.

“The addition of this new small-scale filling capability underlines Catalent’s commitment to our customers with early stage programs looking to accelerate molecules into the clinic,” said Mike Riley, Catalent’s region president, Biologics, North America, in the press release. “The filling line will also be fully leveraged as part of our OneBio offering, an integrated solution for drug substance and drug product development, manufacturing, and clinical supply, enabling faster development timelines to Phase 1 clinical trials and beyond.”

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The facility for early-phase clinical biologics formulation development and drug product fill/finish services will be integrated with an existing Catalent facility nearby.

Catalent Acquires New Biologics Facility in Indiana 

Hovione, a contract development and manufacturing organization, announced on Sept. 23, 2020 that it has signed a partnership agreement with Ligand, a biopharmaceutical company located in San Diego, CA, to increase the production output of Ligand’s Captisol, a chemically modified cyclodextrin used to improve the solubility and stability of drugs, for the formulation of Gilead’s COVID-19 treatment Veklury (remdesivir).

“To meet Captisol demand associated with Veklury, Hovione will soon be producing per month the quantity it usually produces in one year, said Jean-Luc Herbeaux, chief operating officer, Hovione, in a company press release. “This sudden spike in demand has required unique mobilization efforts across the Hovione network to secure additional raw material supply, execute major capital expenditure projects at our sites, maximize operational efficiency, hire additional talent, and identify external partners to expand our overall capacity. The pharmaceutical supply chain is working together in an unprecedented fashion to treat patients and save lives. Hovione is privileged to be part of this truly global response.”

“Ligand values its longstanding partnership with Hovione,” said Matt Foehr, president and chief operating officer of Ligand, in the press release. “Their excellent customer service, global commitment to quality, and high pharmaceutical standards make them an ideal partner for Captisol, a critical component for a number of life-saving medicines. We commend them for responsibly and efficiently partnering with Ligand to manage the scale up and expansion of their operations to contribute to global health during the pandemic.”

The companies plan to increase the production output of Ligand’s Captisol for the formulation of Gilead’s COVID-19 treatment Veklury (remdesivir).

Hovione and Ligand Partner to Increase Production of Captisol for Use in Remdesivir

Johnson & Johnson announced, in a September 23, 2020 press release, the launch of its large-scale, pivotal, multi-country Phase III trial (called Ensemble) for its COVID-19 vaccine candidate, JNJ-78436735, being developed by its Janssen Pharmaceutical Companies. Positive interim results from the company’s Phase I/IIa clinical study demonstrated that the safety profile and immunogenicity after a single vaccination supported further development.

Johnson & Johnson has continued scaling up its manufacturing capacity and remains on track to meet its goal of providing one billion doses of a vaccine each year, the company reported. The company anticipates the first batches of a COVID-19 vaccine to be available for emergency use authorization in early 2021, if proven to be safe and effective.

The Ensemble trial will enroll up to 60,000 adult volunteers in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, and the United States. In order to evaluate the effectiveness of Janssen’s COVID-19 vaccine, countries and clinical trial sites that have a high incidence of COVID-19 and the ability to achieve a rapid initiation will be activated. Participants will include those both with and without comorbidities associated with an increased risk for progression to severe COVID-19. The company said in the press release that it “aims to achieve representation of populations that have been disproportionately impacted by the pandemic in the implementation of its COVID-19 Phase III trial program. In the US, this includes significant representation of Black, Hispanic/Latinx, American Indian, and Alaskan Native participants.”

In addition to this trial of a single-dose regimen, the company announced in an Aug. 14, 2020 press release that it agreed in principle to collaborate with the UK government on a separate Phase III clinical trial in multiple countries to explore a two-dose regimen of Janssen’s vaccine candidate.

“As COVID-19 continues to impact the daily lives of people around the world, our goal remains the same – leveraging the global reach and scientific innovation of our company to help bring an end to this pandemic,” said Alex Gorsky, chairman and CEO, Johnson & Johnson, in the press release. “This pivotal milestone demonstrates our focused efforts toward a COVID-19 vaccine that are built on collaboration and deep commitment to a robust scientific process. We are committed to clinical trial transparency and to sharing information related to our study, including details of our study protocol.”

The vaccine candidate uses the company’s AdVac technology platform, which was also used to develop and manufacture Janssen’s European Commission approved Ebola vaccine and construct its Zika, RSV, and HIV vaccine candidates. The technology platform has been used to vaccinate more than 100,000 people to date across Janssen’s investigational vaccine programs. A vaccine made with the technology is estimated to remain stable for two years at -20 °C and at least three months at 2–8° C, which makes a vaccine candidate compatible with standard vaccine distribution channels.

The company said it continues discussions with national governments and global organizations, as part of its efforts to meet its commitment to make the vaccine candidate accessible globally, provided the vaccine is demonstrated to be safe and effective and following regulatory approval.

A Phase III trial to evaluate safety and efficacy of Janssen’s COVID-19 vaccine candidate, JNJ-78436735, also known as Ad26.COV2.S, is enrolling participants on three continents. 

Johnson & Johnson Launches Multi-Country Phase III Trial of Janssen’s COVID-19 Vaccine Candidate

Aphena Pharma Solutions, a biologics contract manufacturing and packaging company, announced on Sept. 23, 2020 that it has acquired a 500,000 ft2-site in Cookeville, TN, to expand its solid dose division.

The $21-million expansion will provide the company with space to install 24 high-speed bottling lines and eight thermoform blister packaging lines, along with 200,000 ft2of warehouse space for a third-party logistics program, a company press release said. The renovations are expected to be completed by Feb. 1, 2021 and, upon completion, Aphena will move its corporate headquarters to the new location.

“This new facility will make Aphena a top contender in the pharmaceutical contract service space, starting with over 12,000 pallets of cold chain storage capacity,” said Eric Allen, Aphena’s executive vice-president of sales, in the press release. “Being able to offer turnkey packaging and distribution services for biologic products, plus expanding the current operations with newly innovated bottling and packaging lines, will continue to attract key pharmaceutical customers to the middle Tennessee area.”

“This expansion is exciting news for Aphena, our customers and our communities,” added Aphena CEO Shawn Reilley, in the press release. “The solid dose division and recent liquids division expansions will establish Aphena’s position as one of the most diversified manufacturing and packaging companies in the pharmaceutical industry. These growth strategies will continue to offer our customers expanded project capabilities at every level, and it will create a very large employment opportunity, both in Cookeville and at our facility in Easton, Maryland.”

The renovations are expected to be completed by Feb. 1, 2021 and, upon completion, Aphena will move its corporate headquarters to the new location. 

Aphena Pharma Solutions Announces $21-Million Facility Expansion in Tennessee 

Humanigen, a clinical stage biopharmaceutical company, and Thermo Fisher Scientific announced on Sept. 23, 2020 that they are entering into a strategic collaboration to expand manufacturing capacity for Humanigen’s COVID-19 therapeutic candidate, lenzilumab.

Under the terms of the agreement, Thermo Fisher will handle the technical transfer of the lenzilumab bulk drug substance process, with commercial scale production potentially beginning before the end of 2020, a Humanigen press release said.

“Manufacturing preparation, precision, and expertise are critical as we execute on an aggressive strategy, pending a potential EUA [emergency use authorization] from the FDA, to deliver a COVID-19 therapeutic this winter that has the potential to reduce the risk of ventilation or death and send patients home from the hospital earlier,” said Cameron Durrant, MD, CEO of Humanigen, in the press release. “Thermo Fisher provides biologics manufacturing expertise and scalable capacity to further support our production and growth trajectory."

“Effective therapeutics are an important part of the overall approach to curb the arc of the current pandemic and we are committed to enabling leading therapeutic innovations forward for patients through comprehensive supply chain capabilities and expertise,” added Leon Wyszkowski, president, commercial operations for Thermo Fisher’s pharma services business, in the press release.

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Thermo Fisher will handle the technical transfer of the lenzilumab bulk drug substance process, with commercial scale production potentially beginning before the end of 2020.

Thermo Fisher and Humanigen Partner for COVID-19 Therapeutic Candidate

The International Society for Pharmaceutical Engineering (ISPE) has released new guidance on the cleaning validation lifecycle, written by a group of experts and reviewed by regulators and practitioners. The guide’s availability was announced in a Sept. 17, 2020 press release.

“This guide provides the requirements, principles, and practices for cleaning validation in a single volume and is the first of its kind in the industry,” said Jose Caraballo, head Audit Program Management Americas, Corporate Quality Audit and Inspections, Bayer US, Guide co-lead, in the press release. “We decided to address the topic because the expectations for cleaning validation are changing. This guide was written by a group of experts and reviewed by regulators and practitioners in the field. It is a great resource for understanding and applying the principles for compliant cleaning programs, including how-to steps and examples.”

Cleaning Validation Lifecycle—Applications, Methods, and Controls

 covers key areas, such as cleaning methodologies, determination of visual inspection limits, validation of testing and sampling methods, creation of cleaning validation acceptance criteria, and change management. The explanatory and hands-on guidance is available to be purchased online, along with ISPE’s other resources.

ISPE has released new guidance on the cleaning validation lifecycle, written by a group of experts and reviewed by regulators and practitioners.

ISPE Releases Cleaning Validation Guide

Biotechnology company, Moderna, and international research-focused healthcare group, Chiesi Farmaceutici (Chiesi Group), have announced a collaboration aimed at the discovery and development of messenger RNA (mRNA) therapeutics to treat pulmonary arterial hypertension (PAH).

The collaboration, which was announced in a Sept. 16, 2020 press release, will see Moderna leverage its mRNA technology and delivery platforms, alongside Chiesi’s expertise, to lead discovery efforts in PAH biology. Chiesi Group will lead the development and commercialization activities and will have the responsibility of funding the collaborative expenses.

“We are excited to begin this collaboration with Chiesi Group, which provides the opportunity to further leverage our mRNA and delivery technology,” said Stephen Hoge, president of Moderna, in the press release. “This new relationship continues our commitment to partner with companies that have unique expertise in serious diseases, and who share our vision of using mRNA therapeutics to address the unmet needs of patients.”

“Chiesi Group is at the forefront of innovation and discovery of novel therapies for people affected by diseases with high unmet medical need,” added Ugo Di Francesco, CEO of Chiesi Group, in the press release. “And the agreement with Moderna, a leader in mRNA science and delivery, confirms our commitment to better serve patients and healthcare professionals with transformative solutions.”

Under the terms of the collaboration, Moderna will receive a $25 million payment upfront and is eligible for more than $400 million in development, regulatory, and commercial milestones, in addition to tiered double-digit royalties on net sales.

Moderna and Chiesi Group are collaborating on the discovery and development of mRNA therapeutics to treat pulmonary arterial hypertension.

Moderna, Chiesi Group Collaborate on Discovery and Development of mRNA Therapeutics

The Korean Ministry of Food and Drug Safety (MFDS) has given its approval for Celltrion to initiate a Phase II/III trial of its anti-COVID-19 monoclonal antibody treatment candidate, CT-P59, following positive interim results from the Phase I trial.

According to a Sept. 17, 2020 press release, Celtrion had submitted an investigational new drug (IND) application for the clinical trial in six countries and has plans to enroll more than 1000 patients from up to 12 countries. The Phase II/III trial will assess the safety and efficacy to CT-P59 in patients with mild-to-moderate symptoms of SARS-CoV-2 infection.

“Given that COVID-19 represents a significant global threat to life, there is an urgent need to identify treatments that can help stabilize our response to the pandemic. The initiation of the global Phase II/III pivotal trial of CT-P59 is an important step forward, and together with the ongoing Phase I trial in patients with mild symptoms, Celltrion remains committed to investigating a potential anti-COVID-19 monoclonal antibody treatment,” said Dr. Sang Joon Lee, senior executive vice-president of Celltrion, in the press release.

The company has already begun manufacturing the process validation batch of its anti-COVID-19 treatment and has plans to increase manufacturing capacity to meet global and domestic demand.

The Korean MFDS has given its approval for Celltrion to initiate a Phase II/III trial of its anti-COVID-19 monoclonal antibody treatment candidate, CT-P59.

Korean MFDS Approves Celltrion’s IND for Phase II/III Trial of COVID-19 Treatment

AstraZeneca and Samsung Biologics announced on Sept. 22, 2020 that they are entering into a long-term supply agreement for up to $545.6 million.

Under the terms of the agreement, Samsung will offer large-scale commercial manufacturing for drug substance and drug products in support of AstraZeneca’s biologics therapeutics capabilities in the Asia-Pacific region, a Samsung press release said. The deal will start off at $330.8 million with the potential to be increased to $545.6 million.

“This long-term partnership with Samsung Biologics strengthens our manufacturing capabilities, and ensures we are well-positioned to continue to deliver our exciting portfolio of new and established biologics medicines to patients with quality, speed, and efficiency,” said Pam Cheng, executive vice-president, Global Operations and IT, AstraZeneca, in the press release.

“We are very proud to partner with AstraZeneca, a company that uses a rich history of science-led innovation to serve patients,” added Dr. Tae Han Kim, CEO of Samsung Biologics, in the press release. “At Samsung Biologics, our people share this common purpose to help our clients bring innovative solutions to an array of diseases, and we look forward to delivering on our promise to aid in AstraZeneca’s ongoing expansion program.”

Samsung will offer large-scale commercial manufacturing for drug substance and drug products to support AstraZeneca’s biologics therapeutics capabilities in the Asia-Pacific region.

AstraZeneca and Samsung Biologics to Enter into Long-Term Supply Agreement for Up to $545.6 Million

Catalent announced on Sept. 21, 2020 that it has entered into an agreement with T-knife, a Germany-based T-cell company, for the technology transfer and clinical manufacturing of T-knife’s tumor-targeting T1367 T-cell receptor (TCR) program.

Through the agreement, Catalent will use T-knife´s TCR platform for a T-cell receptor-based cell therapy at its Gosselies, Belgium, site in order to manufacture clinical batches for European trials in 2021, a Catalent press release said. T-knife will also transfer the TCR platform to Catalent’s Houston, TX, facility for future clinical trials in North America.

“The product candidates based on our proprietary HuTCR platform require sophisticated, state-of-the-art manufacturing capabilities and deep cell and gene therapy know-how,” said Michael Buchholz, director, Manufacturing, at T-knife, in the press release. “We are convinced that Catalent is the right partner for T-knife to ensure premier manufacturing of our pipeline programs, covering all stages from clinical trials to market.”

“Catalent is well-suited to support T-knife with focused technology transfer and process industrialization in both Gosselies and Houston,” added Manja Boerman, PhD, president, Cell and Gene Therapy, Catalent, in the press release. “Emerging and innovative treatments like T1367 are moving rapidly to the clinic. Catalent is committed to continual investment and expansion to support our clients as they continue on the journey to commercialization.”

Catalent will use T-knife´s TCR platform for a T-cell receptor-based cell therapy at its Gosselies, Belgium, site in order to manufacture clinical batches for European trials in 2021.



Catalent and T-knife Enter into a Technology Transfer and Manufacturing Agreement 

Sanofi and GlaxoSmithKline (GSK) announced on Sept. 18, 2020 that they have signed a purchase agreement with the European Commission to provide up to 300 million doses of the companies’ COVID-19 vaccine, pending regulatory approval.

Under the terms of the agreement, the companies will receive upfront funding from the European Union (EU) for the scale-up of manufacturing capabilities at industrial sites in Belgium, Italy, Germany, and France, a Sanofi press release said. The contract allows for the purchase of the vaccine for all member states of the EU, with the potential to reserve doses for lower- and middle-income countries.

The vaccine candidate uses recombinant protein-based technology used to produce influenza vaccines from Sanofi in combination with GSK’s adjuvant technology, the press release said. Currently, the vaccine is involved in a Phase I/II clinical study with plans for a Phase III study by the end of 2020.

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The companies will receive upfront funding from the European Union for the scale-up of manufacturing capabilities at industrial sites in Belgium, Italy, Germany, and France.



Sanofi and GSK to Provide the EU with 300 Million Doses of its COVID-19 Vaccine Candidate

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

With all eyes on efforts to research and test potential vaccines and therapies to combat the coronavirus pandemic, fears about overly accelerated development programs has heightened demands for wider access to information on study protocols, statistical analysis plans, and early results. One aim is to address concerns that political pressure from the White House might lead to FDA authorization or approval of a COVID-19 vaccine before Phase III data have been fully evaluated.

Leading vaccine manufacturers have responded by taking the unusual step of disclosing full clinical study protocols for their late-stage randomized, blinded, placebo-controlled studies. After the CEO’s of nine companies pledged to collect sufficient data to demonstrate product safety and efficacy before seeking FDA approval, Moderna CEO Stephane Bancel made public its 135-page protocol specifying its plan for randomization of 30,000 patients, how they are selected based on age and likely risk, and listing of all recruitment sites in the United States. The document specifies the plan for blinding, randomized assignment to placebo, efficacy assessments, and statistical analysis plan for determining when the study meets its endpoints and that an independent data monitoring committee is slated to compare efficacy of vaccine to placebo initially when 53 and 106 cases are confirmed, and then after 151 cases of infection. An 

 is slated to compare efficacy of vaccine to placebo initially when 53 and 106 cases are confirmed, and then after 151 cases of infection

Pfizer and AstraZeneca similarly released their trial protocols, acknowledging the need for greater transparency in COVID-19 vaccine research. The Pfizer document specifies the vaccine candidate and dose for Phase II/III testing and the number of trial participants, including age groups and evidence of infection before vaccination. It describes dosing schedule, adverse event assessment, and the plan for interim analyses of data. Here, the sponsor will utilize an internal Pfizer committee to review data plus an external data monitoring committee to review cumulative unblinded data throughout the study. Pfizer 

a total of nearly 44,000 participants, half receiving the vaccine, in anticipation that this will yield 164 primary-endpoint cases within six months

a goal of 50% effectiveness, with statistical confidence to be met when 150 trial participants become ill

. The plan calls for only one interim analysis, compared to more for the other manufacturers, and it might be halted early if the vaccine is 50% effective with fewer cases of contamination.

These disclosures came on the heels of efforts to resolve a report of a serious adverse event in the AstraZeneca trial that halted its Phase III study, generating criticism of the company for failing to reveal specifics on the safety issue, which outside clinicians termed a rare spinal inflammatory disorder called transverse myelitis. Although clinical trials for the vaccine resumed quickly in the United Kingdom, Brazil, and South Africa, US studies remained on hold as officials at the National Institutes of Health (NIH) urged delay pending further investigation into the cause and nature of the adverse event and whether it was triggered by the vaccine or an unhappy coincidence. US authorities said they wanted to examine tissue or blood samples from the British patient to evaluate the case further and hopefully avoid increased vaccine hesitancy in the US.

The disclosure of usually confidential details on research plans responded to concerns raised by leading scientists and research authorities about the need for more transparency in vaccine studies to promote public confidence in the independence and reliability of clinical research on pandemic vaccines and therapies. Although vaccine developers were providing the usual public information on study sites and enrollment plans, experts continued to seek more details on statistical analysis plans that would allow more public assessment of adverse events and research outcomes. And they wanted to know when sponsors were likely to seek input from independent data safety monitoring boards on whether to stop a trial early—either to assess a safety issue or to file an emergency use authorization (EUA) with FDA. With the federal government providing billions in support of vaccine development programs, independent scientists insist that the public should have that kind of information.

Fears about overly accelerated development programs has heightened demands for wider access to information on study protocols, statistical analysis plans, and early results.

COVID-19 Vaccine Concerns Prompt Clinical Trial Transparency

Lonza and Humanigen, a clinical-stage biopharmaceutical company focused on the treatment of immune hyper-response (cytokine storm), announced on Sept. 15, 2020 that they have entered into a strategic collaboration to expand the manufacturing capacity for lenzilumab, a therapeutic candidate for COVID-19 currently in Phase III clinical trials. The partnership for manufacturing expansion is established in advance of a potential Emergency Use Authorization expected in 2020 and subsequent commercialization.

Lenzilumab comes from Humanigen's proprietary Humaneered anti-human granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody (mAb) platform. This mAb has the potential to prevent and treat cytokine storm, which is believed to trigger the acute respiratory distress syndrome in severe cases of COVID-19.

The collaboration between Lonza and Humanigen enables Humanigen to leverage Lonza's mAb manufacturing and regulatory expertise and provides Humanigen with additional capacity for current good manufacturing practices (CGMP) production of lenzilumab. Operations are intended to start in 2021 and production of lenzilumab will begin at Lonza's 2000-L manufacturing facilities in Hayward, CA. Technology transfer is expected to begin in the third quarter of 2020.

"In an effort to change the course of this pandemic, advancing lead COVID-19 therapeutics requires matched supply chain efforts and expertise to meet the continued and urgent patient needs. COVID-19 has highlighted the need for heightened industry collaboration and coordination and we are excited to work closely with Humanigen as we work to combat this global health crisis," said Jean-Christophe Hyvert, chief commercial officer, Lonza, in a company press release.

"We are ramping up our manufacturing efforts for lenzilumab, our lead drug candidate, and this collaboration with Lonza, a global manufacturing leader with expertise in technology transfer and an established track record of working with regulatory bodies for approved and commercialized products, comes at a crucial time to meet production demand for COVID-19 therapeutics this winter," stated Cameron Durrant, MD, CEO, Humanigen, in the press release.

The collaboration will expand the manufacturing capacity for lenzilumab, a COVID-19 therapeutic candidate, in advance of a potential Emergency Use Authorization in 2020.

Lonza, Humanigen Partner to Expand Manufacturing of Lenzilumab for Potential COVID-19 Therapy

On Sept. 15, 2020 Novavax announced an amendment to its existing agreement with Serum Institute of India Private Limited (SIIPL) under which SIIPL will also manufacture the antigen component of Novavax’s COVID‑19 vaccine candidate, NVX‑CoV2373. With this amendment, Novavax will increases its manufacturing capacity for the vaccine candidate to more than two billion doses annually, when all planned capacity has been brought online by mid-2021.

The antigen component of the vaccine candidate is being manufactured at Novavax CZ in Bohumil, Czech Republic (formerly Praha Vaccines), in addition to the following partnered manufacturing sites:

FUJIFILM Diosynth Biotechnologies (FDB), in the United Kingdom and in North Carolina and Texas in the United States (US)

Novavax’s Matrix-M adjuvant, a component of NVX‑CoV2373, is now being manufactured at Novavax AB in Uppsala, Sweden, and in the following partnered manufacturing sites:

PolyPeptide Group, which will manufacture two key intermediaries used in Matrix-M in the US and Sweden

“Signing of the manufacturing agreement with Novavax for NVX-CoV2373 is another great milestone for both companies, which will further strengthen our existing relationship. SIIPL expertise to scale-up and manufacture NVX-CoV2373 will help ensure the supply of this most-needed vaccine,” said Adar Poonawalla, CEO of Serum Institute of India, in a company press release.

“Today’s agreement with Serum Institute enhances Novavax’[s] commitment to equitable global delivery of our COVID-19 vaccine. With this arrangement, we have now put in place a global supply chain that includes the recently acquired Praha Vaccines and partnerships with leading biologics manufacturers, enabling production on three continents,” said Stanley C. Erck, president and CEO of Novavax, in the press release. “We continue to work with extraordinary urgency to develop our vaccine, now in Phase [II] clinical trials, and for which we anticipate starting Phase [III] efficacy trials around the world in the coming weeks.”

The agreement will Increase global manufacturing capacity for Novavax’s vaccine candidate, NVX-CoV2373, to more than two-billion annualized doses when at full capacity in 2021.

Novavax in COVID-19 Vaccine Manufacturing Agreement with Serum Institute of India

On Sept. 17, 2020, Eli Lilly and Company and Amgen announced that they entered into a global antibody manufacturing collaboration that is expected to significantly increase the supply capacity available for Lilly's potential COVID-19 therapies.

Under the collaboration, the two companies will have the ability to quickly scale up production, which will allow them to serve many more patients around the world should one or more of Lilly's antibody therapies prove successful in clinical testing and receive regulatory approval. Lilly is currently involved in studying several potential neutralizing antibodies for the prevention and/or treatment of COVID-19, as either monotherapy or in combination.

"Based on our initial clinical studies, we believe that virus neutralizing antibodies, including LY-CoV-555, could play an important role in the fight against COVID-19," said Daniel Skovronsky, MD, PhD, Lilly's chief scientific officer and president of Lilly Research Laboratories, in a company press release. "Increasing the manufacturing capacity for our neutralizing antibodies through this collaboration with Amgen is a crucial next step, and together we hope to be able to produce many millions of doses even next year."

"We are impressed with Lilly's data, in particular the reduction in hospitalizations, and are enthusiastic about the potential for these neutralizing antibodies as a therapeutic for COVID-19," said David M. Reese, MD, executive vice-president of research and development at Amgen, in the press release.

"We are proud to partner with Lilly and leverage our deep technical expertise in antibody development and, in particular, our strong capabilities in the scale up and manufacturing of complex biologics. This is yet another example of the ways our industry is closely collaborating to combat this devastating disease and help patients around the world access new therapies," added Esteban Santos, executive vice-president of Operations at Amgen, in the press release.

The agreement between the two companies will significantly increase global supply capacity for Lilly's potential COVID-19 treatments.

Lilly and Amgen in Manufacturing Collaboration for COVID-19 Antibody Therapies

, dated Aug. 27, 2020, to Kalchem International after an inspection of the company’s Lindsay, OK, facility found violations of current good manufacturing practices (CGMPs). The inspection was conducted from February 10–21, 2020.

Specifically, according to FDA, the company shipped drug product before receiving the certificate of analysis with assay results from its contract laboratory and batch records were reviewed and approved after the batch was released. The agency requested in the warning letter that the company provide FDA with a list of chemical and microbial specifications used to analyze product batches, an assessment of the company’s laboratory practices and procedures, and a remediation plan to ensure the company’s quality unit (QU) properly functions.

The warning letter also stated that the company’s QU failed to adequately ensure that API met CGMP requirements. Records were not maintained and reviewed for each API that was relabeled, according to FDA. Re-packaging batch records were also not adequately reviewed before release. “For example, one lot of Lidocaine HCL was re-packaged with an incorrect lot number and shipped. Your QU reviewed the Chemical Repackaging record six days after the product had been shipped. The error was not detected until the FDA investigator found it during our inspection,” the letter stated. FDA asked the company to provide a risk assessment of the hazards of inadequate documentation and oversight of relabeled drugs.

The agency sent a warning letter to Kalchem International for CGMP violations found at the company’s Lindsay, OK, facility.

Oklahoma Facility Given FDA Warning

 on Sept. 18, 2020 that its human medicines committee (CHMP) has recommended approval for Exparel (bupivacaine), for the treatment of post-operative pain; MenQuadfi (meningococcal group A, C, W and Y conjugate vaccine), to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W and Y; and Supemtek (Quadrivalent Influenza Vaccine). Market authorization under exceptional circumstances was recommended for the anthrax treatment, Obiltoxaximab SFL (obiltoxaximab). CHMP also gave a positive opinion to the biosimilar Nyvepria (pegfilgrastim) “for reducing the duration of neutropenia and the incidence of febrile neutropenia in patients treated with cytotoxic chemotherapy.”

Market authorization was recommended for the anticoagulant Rivaroxaban Accord (rivaroxaban). Rivaroxaban Accord is a generic drug used to treat and prevent venous thromboembolism, pulmonary embolism, and the prevention of atherothrombotic events. Marketing authorization was also recommended for Phelinun (melphalan) for treatment of “certain haematological and other cancers and as reduced intensity conditioning treatment prior to allogeneic haematopoietic stem cell transplantation in haematological diseases in adults and children. Hybrid applications rely in part on the results of pre-clinical tests and clinical trials of an already authorized reference product and in part on new data,” according to an EMA press release.

CHMP also gave 15 recommendations on extensions of therapeutic indication, includingDeltyba, Flucelvax Tetra, Fycompa, Lynparza, Opdivo, Symkevi, Tecentriq, Velphoro, Yervoy, Zavicefta, Zejula and two extensions of indication for Kalydeco. The committee recommended an extension of indication to Olumiant (baricitinib), to include thetreatment of moderate to severe atopic dermatitis in adult patients who are candidates for systemic therapy. Orfadin (nitisinone)was recommended for an extension of indication to include the treatment of alkaptonuria in adults.

During its September 2020 meeting, CHMP also confirmed its April 2020 opinion on the suspension of all ranitidine drugs in the European Union because of N-nitrosodimethylamine (NDMA) impurity.

The EMA recommendations include a meningococcal vaccine and the biosimilar Nyvepria.

EMA Recommends Seven Medicines for Approval

The Russian Direct Investment Fund (RDIF) has announced three deals with India, Brazil, and Mexico, during the first half of September 2020, for the supply of doses of Sputnik V, a potential COVID-19 vaccine that is currently undergoing early clinical trials.

On Sept. 9, 2020, RDIF released information on the first supply deal, which was struct with Landsteiner Scientific pharmaceutical company and involves the supply of 32 million doses of Sputnik V to Mexico. According to the release, deliveries are expected to commence in November 2020, subject to approval of the vaccine by Mexico’s regulators

A deal between RDIF and the State of Bahia (Brazil) was then announced on Sept. 11, 2020. Under the terms of this deal, RDIF has agreed to supply up to 50 million doses of the Russian vaccine to Brazil, starting in November 2020, if the Brazilian regulators issue an approval.

The most recent deal was announced in a press release on Sept. 16, 2020, and was struck with Dr. Reddy’s Laboratories in India. Through this deal, Dr. Reddy’s will cooperate on clinical trials and distribution of 100 million doses of Sputnik V in India, once regulatory approval in the country has been granted.

These deals follow on from the publication of Phase I/II data from open, non-randomized studies that were published in 

 (1). The studies were performed in Russian hospitals and included 76 healthy adults, with reported strong immune responses seen in all participants. However, multiple scientists have co-signed an open letter to the study authors and 

over concerns about the reliability of the data presented in the study (2). To date, the study authors have not issued a formal response to the open letter.

The Russian Direct Investment Fund has announced three deals with India, Brazil, and Mexico, for the supply of doses of Sputnik V, a potential COVID-19 vaccine.

Russia Completes Deals with India, Mexico, and Brazil for Sputnik V

 on Sept. 15, 2020 that provides recommendations for the content and placement of geriatric information in labeling of prescription drugs. The guidance is meant to ensure consistent placement of this type of information in the correct sections and subsections in labeling so that it is clear and accessible to healthcare practitioners.

The draft guidance document replaces a withdrawn guidance, 

Content and Format for Geriatric Labeling 

(October 2001), and gives examples of geriatric use statements in labeling and examples of when FDA may permit applicants to omit or revise required information. In the document, the agency discusses labeling when a drug is approved for general use by adults, including geriatric patients; a drug is approved for geriatric-specific indications; and a drug is not approved for geriatric patient use.

The guidance document offers information on the placement and content of geriatric information in labeling of drugs and biologics.

FDA Gives Guidance on Geriatric Information in Labeling

Eli Lilly and Company and Amgen announced on Sept. 17, 2020 that they are entering into a global antibody manufacturing collaboration to expand Eli Lilly’s supply capacity for potential COVID-19 therapies.

Under the terms of the partnership, the companies will be able to scale up production and serve more patients if Eli Lilly’s potential COVID-19 antibody therapies are deemed effective in clinical trials and gain regulatory approval, an Eli Lilly press release said.

"Based on our initial clinical studies, we believe that virus neutralizing antibodies, including LY-CoV-555, could play an important role in the fight against COVID-19," said Daniel Skovronsky, MD, PhD, Eli Lilly's chief scientific officer and president of Lilly Research Laboratories, in the press release. "Increasing the manufacturing capacity for our neutralizing antibodies through this collaboration with Amgen is a crucial next step, and together we hope to be able to produce many millions of doses even next year."

"We are proud to partner with Lilly and leverage our deep technical expertise in antibody development and, in particular, our strong capabilities in the scale up and manufacturing of complex biologics,” added Esteban Santos, executive vice-president of operations at Amgen, in the press release. “This is yet another example of the ways our industry is closely collaborating to combat this devastating disease and help patients around the world access new therapies."

The companies aim to scale up production of Eli Lilly’s potential COVID-19 antibody therapies, pending regulatory approval.